Cyclophosphamide has been shown to be an effective agent in the control of neoplasia. This drug, however, is immunosuppressive at doses used for effective chemotherapy. The full potential of cellular immune reactivity toward antigenic tumor cells is therefore compromised by cyclophosphamide therapy. I have found that high single doses of cyclophosphamide suppress the generation of cytotoxic T cells in vitro. This inhibited cytotoxic response is not due to the elimination of cytotoxic precursor cells but occurs through the inactivation of accessory thymus cells needed for an effective cytotoxic T-cell response. The objectives of this proposal are to characterize and isolate the active accessory cell which restores immune reactivity in vitro to cyclophosphamide-pretreated effector cells. In addition, both unfractionated thymocytes and enriched accessory cell populations will be used in an adoptive-immunotherapy schedule to enhance cytotoxic activity in vivo in tumor-bearing mice treated with cyclophosphamide. Both cyclophosphamide and accessory cells will be used as therapy for transplantable and spontaneous tumor systems in vivo. It is proposed that adoptive immunotherapy with syngeneic or allogeneic accessory cells will counteract cyclophosphamide-induced suppression of cytotoxic T-cell generation and thereby enhance host immune reactivity against syngeneic tumor cells in vivo.